Current and Future Gene Therapy for Malignant Gliomas

Malignant gliomas are the most common neoplasm in the central nervous system. When treated with conventional treatments including surgery, irradiation, and chemotherapy, the average life expectancy of the most malignant type, glioblastoma multiforme is usually less than 1 year. Therefore, gene therapy is expected to be an effective and possibly curative treatment. Many gene therapeutic approaches have demonstrated efficacy in experimental animal models. However, the current clinical trials are disappointing. This review focuses on current therapeutic genes/vectors/delivery systems/targeting strategies in order to introduce updated trends and hopefully indicate prospective gene therapy for malignant gliomas

Nuclear export of OLIG2 in neural stem cells is essential for ciliary neurotrophic factor–induced astrocyte differentiation

Neural stem cell (NSC) differentiation is precisely controlled by a network of transcription factors, which themselves are regulated by extracellular signals (Bertrand et al., 2002; Shirasakiand and Pfaff, 2002). One way that the activity of such transcription factors is controlled is by the regulation of their movement between the cytosol and nucleus (Vandromme et al., 1996. Lei and Silver, 2002). Here we show that the basic helix–loop–helix transcription factor OLIG2, which has been shown to be required for motor neuron and oligodendrocyte development, is found in the cytoplasm, but not the nucleus, of astrocytes in culture and of a subset of astrocytes in the subventricular zone. We demonstrate that the accumulation of OLIG2 in the nucleus of NSCs blocks the CNTF-induced astrocyte differentiation and that the translocation of OLIG2 to the cytoplasm is promoted by activated AKT. We propose that the AKT-stimulated export of OLIG2 from the nucleus of NSCs is essential for the astrocyte differentiation

Configuration of the active Mg-ATP complex in protein kinase C reaction

AbstractTo probe the active site structure of protein kinase C stereochemical studies were carried out by using ATPβs. The enzyme utilizes either one of the diastereomers (Sp and Rp) of ATPβs almost equally well as a substrate. This result contrasts with that for cyclic AMP-dependent protein kinase, suggesting that the topography of the nucleotide-binding site is significantly different between the two kinases

Video-Rate Bioluminescence Imaging of Matrix Metalloproteinase-2 Secreted from a Migrating Cell

Background: Matrix metalloproteinase-2 (MMP-2) plays an important role in cancer progression and metastasis. MMP-2 is secreted as a pro-enzyme, which is activated by the membrane-bound proteins, and the polarized distribution of secretory and the membrane-associated MMP-2 has been investigated. However, the real-time visualizations of both MMP-2 secretion from the front edge of a migration cell and its distribution on the cell surface have not been reported. Methodology/Principal Findings: The method of video-rate bioluminescence imaging was applied to visualize exocytosis of MMP-2 from a living cell using Gaussia luciferase (GLase) as a reporter. The luminescence signals of GLase were detected by a high speed electron-multiplying charge-coupled device camera (EM-CCD camera) with a time resolution within 500 ms per image. The fusion protein of MMP-2 to GLase was expressed in a HeLa cell and exocytosis of MMP-2 was detected in a few seconds along the leading edge of a migrating HeLa cell. The membrane-associated MMP-2 was observed at the specific sites on the bottom side of the cells, suggesting that the sites of MMP-2 secretion are different from that of MMP-2 binding. Conclusions: We were the first to successfully demonstrate secretory dynamics of MMP-2 and the specific sites for polarized distribution of MMP-2 on the cell surface. The video-rate bioluminescence imaging using GLase is a useful method t

Rate of Heat Transfer between a Fluidized Bed and the Tube Wall at Higher Temperature

The heat transfer coefficient between a fluidized bed and the tube wall, hw, was measured in the temperature range of 500° to 800°C. Quartz and fused alumina particles were fluidized in the air stream. The coefficient hw was obtained between 70 and 800 kcal/m²·hr·°C. It increases with the flow rate of air. The effects of bed temperature and heat content and size of the particles on hw were imperceptible. By comparing the heat transfer coefficients obtained in this work with those at lower temperatures below 200°C, the difference between both coefficients was not significant

Medical Image Diagnosis of Lung Cancer by Deep Feedback GMDH-Type Neural Network

The deep feedback Group Method of Data Handling (GMDH)-type neural network is applied to the medical image diagnosis of lung cancer. The deep feedback GMDH-type neural network can identified very complex nonlinear systems using heuristic self-organization method which is a type of evolutionary computation. The deep neural network architectures are organized so as to minimize the prediction error criterion defined as Akaike’s Information Criterion (AIC) or Prediction Sum of Squares (PSS). In this algorithm, the principal component-regression analysis is used for the learning calculation of the neural network. It is shown that the deep feedback GMDH-type neural network algorithm is useful for the medical image diagnosis of lung cancer because deep neural network architectures are automatically organized using only input and output data

Medical Image Analysis of Brain X-ray CT Images By Deep GMDH-Type Neural Network

The deep Group Method of Data Handling (GMDH)-type neural network is applied to the medical image analysis of brain X-ray CT image. In this algorithm, the deep neural network architectures which have many hidden layers and fit the complexity of the nonlinear systems, are automatically organized using the heuristic self-organization method so as to minimize the prediction error criterion defined as Akaike’s Information Criterion (AIC) or Prediction Sum of Squares (PSS). The learning algorithm is the principal component-regression analysis and the accurate and stable predicted values are obtained. The recognition results show that the deep GMDH-type neural network algorithm is useful for the medical image analysis of brain X-ray CT images

Correlation of antinuclear antibody and anti-double-stranded DNA antibody with clinical response to infliximab in patients with rheumatoid arthritis: a retrospective clinical study

[Introduction]The induction of antinuclear antibodies (ANAs) or anti-double-stranded (ds) -DNA antibodies (Abs) after infliximab (IFX) therapy in rheumatoid arthritis (RA) is a well-known phenomenon, but the correlation of such Abs with the clinical response to IFX has not yet been determined. The aims of this retrospective observational study were to examine the prevalence of positive ANA and anti-ds-DNA Abs before and after IFX therapy in patients with RA and to investigate whether an increased titer of such Abs is associated with the clinical efficacy of IFX. [Methods]One hundred eleven RA patients who had received IFX were studied. ANA (indirect immunofluorescence with HEp-2 cells) and anti-ds-DNA Abs (Farr assay) results were examined before and after IFX therapy. [Results]The overall clinical response assessed by EULAR response criteria was as follows: good response in 55%, including remission in 38%; moderate response in 18%; and no response (NOR) in 27%. The positivity of ANA (≥ 1:160) and anti-ds-DNA Abs significantly increased from 25% to 40% (P = 0.03) and from 3% to 26% (P < 0.001) after IFX, respectively. EULAR response differed significantly according to the ANA titer before IFX (P = 0.001), and the efficacy of IFX became worse as the ANA titer before starting IFX increased. Furthermore, the differences in the clinical response of the ANA titer before IFX ≤ 1:80 and ≥ 1:160 were significant (good, moderate, and no response were 66%, 9%, and 25% in ≤ 1:80 group versus 26%, 33%, 41% in ≥ 1:160 group, respectively; P < 0.001). In 13 patients whose ANA had increased after IFX, 10 showed NOR, only one showed a good response, and none reached remission. These clinical responses were significantly different from ANA no-change patients. In 21 patients with positive anti-ds-DNA Abs after IFX, 16 showed NOR, only two showed a good response, and none reached remission. [Conclusions]The present study suggests that the ANA titer before starting IFX predicts the clinical response to IFX. The increased titers of ANA or anti-ds-DNA Abs after IFX may be useful markers of NOR